The ability to detect the sentinel lymph nodes (SLNs) associated with dermatologic malignancies is essential in the management of such malignancies. SLN mapping is important for staging and to determine the use of adjuvant therapies. A number of methods have been developed to detect the SLN, with the currently used techniques being peritumoral injection of radiolabeled (Tc-99m) sulfur colloids (i.e., lymphoscintigraphy) or blue dyes. While the use of lymphoscintigraphy and blue dye is accurate in demonstrating the SLN, the sensitivity is still less than 95 % and the resolution is such that it is impossible to demonstrate the internal architecture of the SLN, which may be important for the detection of metastatic nodes (in the SLN as well as in secondary nodes). Thus, this project proposes the development of a minimally invasive methodology for SLN detection and assessment of nodal status by peritumoral injection of a microbubble based ultrasound contrast agent followed by non-invasive, real-time ultrasound imaging (US) of the microbubbles draining within the lymphatics. If successful this new method will provide not only anatomical information, but also the potential for minimally invasive assessment of SLN status. A naturally occurring swine melanoma model will be studied to determine the accuracy of contrast US SLN detection and to compare the new method to lymphoscintigraphy using blue dye for SLN identification as the gold standard. Three-dimensional (3D) US data will be obtained to measure the volume of the primary tumor, as well as the volume of the SLNs and metastatic tumor within the SLNs. The results will be compared to histopathological assessment of lymph node status [including ribonucleic acid (RNA) extraction and analysis] as the gold standard.